The broad objectives of this project are to study regulatory mechanisms of pyrimidine biosynthesis accompanying cellular proliferation in normal and neoplastic colonic cells. These objectives are being pursued by kinetic studies of key regulatory enzymes of the de novo and salvage pathways of pyrimidine biosynthesis, by the determination of flux-rates through these pathways and by application of selective inhibitors for determining effects on cellular proliferation. These studies are to be carried out in both in vivo and in vitro systems using normal and neoplastic mouse colonic tissues (dimethylhydrazine-induced neoplasia) as well as an established human colonic cancer cell line (HT-29).